A-to-I RNA editing is a widespread post-transcriptional modification event in vertebrates. It could increase transcriptome and proteome diversity through recoding the genomic information and cross-linking other regulatory events, such as those mediated by alternative splicing, RNAi and microRNA (miRNA). Previous studies indicated that RNA ...
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The first discoveries of mammalian A-to-I RNA editing have been serendipitous. In conjunction with the fast advancement in sequencing technology, systematic methods for prediction and detection of editing sites have been developed, leading to the discovery of thousands of A-to-I editing sites. ...
Evidence for the chemical conversion of adenosine-to-inosine (A-to-I) in messenger RNA (mRNA) has been detected in numerous metazoans, especially those "most successful" phyla: Arthropoda, Mollusca, and Chordata. The requisite enzymes for A-to-I editing, ADARs (adenosine deaminases acting on RNA) are highly conserved and are present in ...
Carcinogenesis is a complex, multi-stage process depending on both endogenous and exogenous factors. In the past years, DNA mutations provided important clues to the comprehension of the molecular pathways involved in numerous cancers. Recently, post-transcriptional modification events, such as RNA editing, are emerging as new players in several human diseases, including ...
The molecular mechanism and physiological function of recoding by A-to-I RNA editing is well known, but its evolutionary significance remains a mystery. We analyzed the RNA editing of the Kv2 K+ channel from different insects spanning more than 300 million years of evolution: Drosophila melanogaster, Culex pipiens (Diptera), Pulex ...
miRNA Editing--We Should Have Inosine This Coming Jeffrey W. Habig,1,2,3 Taraka Dale,1 the first evidence that editing of a microRNA (miRNA) precursor by ADARs can modulate the target specificity is through adenosine-to-inosine (A-to-I) editing, a reaction catalyzed by adenosine deaminases that act
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Evidence for large diversity in the human transcriptome created by Alu RNA editing Michal Barak1-to-I) RNA editing alters the original genomic content of the human transcriptome and is essential for maintenance of normal life in mammals. A-to-I editing in Alu repeats is abundant in the human genome
RNA editing by deamination of adenosine to inosine (A-to-I editing) is a physiologically important posttranscriptional mechanism that can regulate expression of genes by modifying their transcripts. A-to-I editing is mediated by adenosine deaminases acting on RNA (ADAR) that can catalytically ...
RNA editing enhances the diversity of gene products at the post-transcriptional level. Approaches for genome-wide identification of RNA editing face two main challenges: separating true editing sites from false discoveries and accurate estimation of editing levels. We developed an approach to analyze transcriptome ...
A-to-I RNA editing, the deamination of adenosine (A) to inosine (I) that occurs in regions of RNA with double-stranded character, is catalyzed by a family of Adenosine Deaminases Acting on RNA (ADARs). In mammals there are three ADAR genes. Two encode proteins that possess demonstrated deaminase activity: ADAR1, which is interferon-inducible, and ADAR2 ...
Adenosine deaminases acting on RNA (ADARs) catalyze adenosine (A) to inosine (I) editing of RNA that possesses double-stranded (ds) structure. A-to-I RNA editing results in nucleotide substitution, because I is recognized as G instead of A both by ribosomes and by RNA polymerases. A-to-I substitution can also cause ...
The post-transcriptional modification of mammalian transcripts by A-to-I RNA editing has been recognized as an important mechanism for the generation of molecular diversity and also regulates protein function through recoding of genomic information. As the molecular players of editing are characterized and an increasing number of genes become identified ...
Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA molecules to inosines, which are functionally equivalent to guanosines. Recently, global approaches to studying this widely conserved phenomenon have emerged. The use of bioinformatics, high-throughput ...
RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both ...
The complexity of multicellular organisms requires both an increase in genetic information and fine tuning in regulation of gene expression. One of the mechanisms responsible for these functions is RNA editing. RNA editing is a complex process affecting the mechanism of changes in transcriptome sequences. The best studied example of this process is A-to-I ...
RNA editing by adenosine deamination fuels the generation of RNA and protein diversity in eukaryotes, particularly in higher organisms. This includes the recoding of translated exons, widespread editing of retrotransposon-derived repeat elements and sequence modification of microRNA (miRNA) transcripts. Such changes can bring about specific amino acid ...
The serotonin receptor 5HT2CR pre-mRNA is subject to adenosine deamination (RNA editing) at five residues located within a 15 nucleotide stretch of the coding region. Such changes of adenosine to inosine (A-to-I) can produce 32 mRNA variants, encoding 24 different protein isoforms, some of which vary in biochemical and pharmacological properties. Because ...
Adenosine-to-inosine (A-to-I) RNA editing was recently shown to be abundant in the human transcriptome, affecting thousands of genes. Employing a bioinformatic approach, we identified significant global hypoediting of Alu repetitive elements in brain, prostate, lung, kidney, and testis tumors. Experimental validation confirmed this finding, showing ...
ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine (A-to-I). ADAR2 contains two tandem double-stranded RNA-binding motifs (dsRBMs) that are not only important for efficient editing of RNA substrates but also necessary for ...
ADAR1 (adenosine deaminase acting on RNA) catalyzes the conversion of adenosine to inosine, a process known as A-to-I editing. Extensive A-to-I editing has been described in viral RNAs isolated from the brains of patients persistently infected with measles virus, although the precise role of ADAR during measles virus infection remains ...
Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing ...
Adenosine-to-inosine editing in the anticodon of tRNAs is essential for viability. Enzymes mediating tRNA adenosine deamination in bacteria and yeast contain cytidine deaminase-conserved motifs, suggesting an evolutionary link between the two reactions. In trypanosomatids, tRNAs undergo both cytidine-to-uridine and adenosine-to-inosine editing, but the ...
BackgroundAdenosine to inosine (A-to-I) RNA-editing is an essential post-transcriptional mechanism that occurs in numerous sites in the human transcriptome, mainly within Alu repeats. It has been shown to have consistent levels of editing across individuals in a few targets in the human brain and altered in several human pathologies. ...
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by preventing the translation of specific messenger RNAs. Adenosine deaminases acting on RNAs (ADARs) catalyze adenosine-to-inosine (A-to-I) RNA editing, the conversion of adenosines into inosines, in double-stranded RNAs. Because inosine preferentially base pairs with cytidine, ...
Site-specific deamination of five adenosine residues in the pre-mRNA of the serotonin 2C receptor, 5HT2CR, alters the amino acid sequence of the encoded protein. Such RNA editing can produce 32 mRNA variants, encoding 24 protein isoforms that vary in biochemical and pharmacological properties. Because serotonin functions in the regulation of mood and behaviour, modulation of ...
ADAR2, a member of the adenosine deaminase family of proteins, is the enzyme that edits the Q/R site in the GluR-B transcript, an important physiological A-to-I editing event. ADAR2 pre-mRNA undergoes a number of known alternative splicing events, affecting its function. Here we describe a novel alternatively spliced exon, located ...
The central dogma of molecular biology defines the major route for the transfer of genetic information from genomic DNA to messenger RNA to three-dimensional proteins that affect structure and function. Like alternative splicing, the post-transcriptional conversion of adenosine to inosine (A-to-I) by RNA editing can dramatically expand the diversity of the ...
We show here that expression of genes from convergent transcription units can be regulated by the formation of double-stranded RNA (dsRNA) in the region of overlapping polyadenylation signals. The model system employed is the mouse polyomavirus. The early and late genes of polyomavirus are transcribed from opposite strands of the circular viral genome. At early times after infection, the early ...
SENSING APPROACH TO SIGINT PROCESSING DARPA A-to-I Grant N66001-06-1-2009 "Dr. Healy manages several. Wegman � Bill May A COMPRESSED SENSING APPROACH TO SIGINT PROCESSING DARPA A-to-I Grant N66001
Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in ...
Human and chimpanzee genomes are almost identical, yet humans express higher brain capabilities. Deciphering the basis for this superiority is a long sought-after challenge. Adenosine-to-inosine (A-to-I) RNA editing is a widespread modification of the transcriptome. The editing level in humans is significantly higher compared with ...
The pre-mRNA encoding the serotonin 2C receptor, HTR2C (official mouse gene symbol, Htr2c), is subject to adenosine deamination that produces inosine at five sites within the coding region. Combinations of this site-specific A-to-I editing can produce 32 different mRNA sequences encoding 24 different protein isoforms with differing biochemical and ...
The role of epigenetics in tumor onset and progression has been extensively addressed. Discoveries in the last decade completely changed our view on RNA. We now realize that its diversity lies at the base of biological complexity. Adenosine-to-inosine (A-to-I) RNA editing emerges a central generator of transcriptome diversity and regulation in higher ...
One type of RNA editing involves the deamination of adenosine (A) residues to inosines (I) at specific sites in specific pre-mRNAs. These inosines are subsequently read as guanosines by the ribosome, with potentially significant consequences for protein sequence. In mammals, two such A-to-I RNA editases are RED1, which edits some serotonin and glutamate ...
Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission and play roles in many cognitive processes. They are under intense research as potential targets of drugs used to treat neurodegenerative diseases and neurological disorders such as Alzheimer's disease and schizophrenia. Invertebrate nAChRs are targets of anthelmintics as well as a major group of ...
The DRADA gene in mammals encodes an A-to-I RNA editase, an adenosine deaminase that acts on pre-mRNAs to produce site specific inosines. DRADA has been shown to deaminate specific adenosine residues in a subset of glutamate and serotonin receptors, and this editing results in proteins of altered sequences and functional properties. DRADA thus plays a role in creating protein ...
BackgroundThe serotonin 5-HT2C receptor (5-HT2CR) is expressed in amygdala, a region involved in anxiety and fear responses and implicated in the pathogenesis of several psychiatric disorders such as acute anxiety and post traumatic stress disorder. In humans and in rodent models, there is evidence of both anxiogenic and anxiolytic actions of ...
Human mitochondrial tRNA (hmt-tRNA) mutations are associated with a variety of diseases including mitochondrial myopathies, diabetes, encephalopathies, and deafness. Because the current understanding of the precise molecular mechanisms of these mutations is limited, there is no efficient method to treat their associated mitochondrial diseases. Here, we use a variety of known mutations in ...
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